PROJECT SUMMARY/ABSTRACT - OVERALL The principal aim of the UC Davis ADC (UCD ADC) is to measure trajectories of cognitive change and transition to dementia among a carefully studied and highly diverse subject cohort in order identify modifiable risk and protective factors with the ultimate goal of developing novel interventions to improve cognitive health and prevent dementia. This principal aim is accomplished through recruitment, maintenance and longitudinal follow up to autopsy of a cohort of subjects from both community and clinical referral sources that varies along the spectrum of cognitive ability, race/ethnicity, educational achievement, social economic status, spoken language and degrees of medical comorbidity. To accomplish this principal aim, the UCD ADC utilizes six highly integrated resource cores and a research education component to create a strong research infrastructure while emphasizing a highly collaborative environment to facilitate novel research efforts, education and training. In addition, UCD ADC encourages researcher diversity through the newly developed Latino Aging Research Resource Center (LARRC) a NIA Resource Center in Minority Aging Research (RCMAR) program. This highly diverse and predominantly cognitively normal cohort was developed to pursue four major scientific themes: 1) identify the earliest clinical and biological evidence of age-related dementing diseases, 2) identify and evaluate protective factors with emphasis on developing strategies to increase cerebral reserve or resistance to age-related degenerative diseases, 3) examination of the impact of mixed pathological processes on cognitive decline and conversion to dementia and 4) discovery and evaluation of biological markers of cognitive health or decline. In line with the pressing need to develop novel clinical therapeutics for AD, the UCD ADC also has begun to support investigator sponsored therapeutic studies. This work, performed in a highly collaborative and inclusive environment that fully utilizes the unique resources of the UC Davis environment and the skills of our collaborators, not only aims to advance new scientific knowledge, but also encourages new and innovative research, improved clinical diagnoses, training, patient and community education and superb data management and data sharing to leverage ongoing activities of the UCD ADC to the wider research and educational community. To obtain these objectives, the overall specific aims of the UCD ADC are to: Provide an environment and core resources to enhance cutting-edge research as well as encouraging extensive use of these resources by basic science, biomedical, behavioral, social and clinical investigators. Manage these resources ethically, responsibly and efficiently through a well-established and highly effective administrative structure that seeks to foster new and innovative areas of research and treatments. Provide investigators and research groups with a unique resource of well-characterized patients and control subjects through recruitment, retention and comprehensive assessment of a highly diverse cohort. Provide a rich training environment for students, fellows and junior faculty to acquire research skills and experience in interdisciplinary aging and dementia research as well as mentor new and diverse faculty members. Respond effectively to national needs related to AD and associated dementing disorders by timely submission of NACC reports, support of NACC data acquisition through MRI analyses and DNA submissions. Educate individuals across the knowledge spectrum from medical professionals to the lay public and share new scientific information developed at the UCD ADC with NIA stakeholders. Continue dementia advocacy in collaboration with the Alzheimer's Association at local, national and international levels, as well as supporting the NIA through service on various committees.